Keratinocytes are born spherical in the deep basal layer and die flattened with a larger en face diameter in the superficial stratum corneum. Since chromatin filaments in nuclei are too small to scatter light efficiently, nuclei in keratinocytes appear dark. In the spinous and granular layers of the epidermis, the en face distribution of keratinocytes is grid-like, with a regular spatial frequency. Nuclei present as dark centroids in the grid. Since organelles and intercellular tissue constituents are comparably sized to the illumination wavelength and are of high refractive index relative to the surrounding medium, they provide bright contrast to the grid between nuclei in a characteristic honeycomb pattern.
The absence of the normal honeycomb pattern of epidermal keratinocytes has sensitivity and specificity of 87.5% and 52.1%, respectively for melanoma detection with the human eye. The pattern of keratinocytes is even more important in distinguishing between actinic keratoses and normal skin. Finally, the abundance of keratinocytes may be a target for cosmetic skin products.